Affiliation(s):
Centre for Blood Research
Canadian Blood Service – Centre for Innovation
Location:
UBC Life Sciences Centre

Short Bio:

Dr. Pryzdial’s doctoral work was on the physical biochemistry of complement protein interactions at the University of Toronto. Although staying in blood protein research, postdoctoral training at the NIH Specialized Centre of Research in Thrombosis, University of Vermont shifted his interests to blood clotting biochemistry. Joining Canadian Blood Services (at that time part of the Red Cross Society) and University of Ottawa in 1990/91, he transferred his laboratory in 2001 to become a member of the UBC Centre for Blood Research. Dr. Pryzdial’s lab members investigate: the regulation of clot formation and how it dissolves; how viruses exploit blood proteins to enhance cellular infection; and the molecular basis of patients with clotting protein deficiency. Particular emphasis is placed on novel applications of plasma proteins to transfusion science and advancing our understanding of heart disease. (www.blood.ca, www.cbr.ubc.ca)

Academic Backgrounds:
  • PhD, University of Toronto, Biochemistry. 1987
  • BSc, University of Toronto, Biology (Major), Chemistry (Minor), Biochemistry, Specialist. 1981
Selected Publications
  • Martínez-Gutierrez F, Thi EP, Silverman JM, de Oliveira CC, Svensson SL, Vanden Hoek A, Sánchez EM, Reiner NE, Gaynor EC, Pryzdial EL, Conway EM, Orrantia E, Ruiz F, Av-Gay Y, Bach H. Antibacterial activity, inflammatory response, coagulation and cytotoxicity effects of silver nanoparticles. Nanomedicine. 2011 Jun 27.
  • Talbot K, Song J, Hewitt J, Serrano K, Ho M, Carter CJ, MacGillivray RT, Pryzdial EL. A novel compensating mechanism for homozygous coagulation factor V deficiency suggested by enhanced activated partial thromboplastin time after reconstitution with normal factor V. Br J Haematol. 2010 Oct;151(2):198-200.
  • Gershom ES, Sutherland MR, Lollar P, Pryzdial EL. Involvement of the contact phase and intrinsic pathway in herpes simplex virus-initiated plasma coagulation. J Thromb Haemost. 2010 May;8(5):1037-43. Epub 2010 Jan 30.
  • Talbot K, Meixner SC, Pryzdial EL. Enhanced fibrinolysis by proteolysed coagulation factor Xa. Biochim Biophys Acta. 2010 Apr;1804(4):723-30.
  • Song J, Talbot K, Hewitt J, MacGillivray RT, Pryzdial EL. Differential contributions of Glu96, Asp102 and Asp111 to coagulation factor V/Va metal ion binding and subunit stability. Biochem J. 2009 Aug 13;422(2):257-64.
  • Churg A, Wang X, Wang RD, Meixner SC, Pryzdial EL, Wright JL. Alpha1-antitrypsin suppresses TNF-alpha and MMP-12 production by cigarette smoke-stimulated macrophages. Am J Respir Cell Mol Biol. 2007 Aug;37(2):144-51.
  • Sutherland MR, Friedman HM, Pryzdial EL. Thrombin enhances herpes simplex virus infection of cells involving protease-activated receptor 1. J Thromb Haemost. 2007 May;5(5):1055-61.
  • Grundy JE, Hancock MA, Meixner SC, Mackenzie RC, Koschinsky ML, Pryzdial EL. Plasminogen binds to plasmin-modulated factor Xa by Ca (2+) – and C-terminal lysine-dependent and -independent interactions. Thromb Haemost. 2007 Jan;97(1):38-44.
  • Derry MC, Sutherland MR, Restall CM, Waisman DM, Pryzdial EL. Annexin 2-mediated enhancement of cytomegalovirus infection opposes inhibition by annexin 1 or annexin 5. J Gen Virol. 2007 Jan;88(Pt 1):19-27.
Research:
  • Blood Proteins
  • Coagulation and Fibrinolysis
  • Role of Blood Proteins in Viral Infection

 

The general expertise in our laboratory is the function of blood proteins and there novel application. By combining biochemistry and molecular engineering, we have discovered new functions of several proteins with possible therapeutic or diagnostic applications to heart disease and virus infection. Our long-range goal is to understand how these findings may impact on other blood protein functions and thereby contribute to optimizing the value derived from blood constituents and their substitutes.

Communication Between Clot-Forming and Clot-Dissolving Proteins

Clot generation (coagulation) and subsequent clearance (fibrinolysis) are fundamental biological processes. A high degree of communication between these opposing pathways is necessary to ensure that clots form and dissolve sequentially, and only when needed. The biological effector of coagulation, thrombin, is activated by an enzyme complex consisting of the protease factor Xa (FXa) and its cofactor Va (FVa). In recent work, Dr. Pryzdial’s group identified a previously unknown mechanism of communication between these clotting factors and the fibrinolysis pathway. The data revealed that FXa and FVa accelerate the clot-buster, tissue plasminogen activator (tPA), which is used as an important therapeutic. These studies suggest that the current fibrinolysis dogma must be revised to include auxiliary tPA cofactors, such as FXa and FVa, in the vicinity of the clot to further understand vascular health and pathology.

Blood Proteins Exploited by Viruses

For decades many viruses have been linked to heart disease. To understand the molecular basis of the clinical correlation, Dr. Pryzdial’s group found that at least herpes simplex virus type 1 and type 2, and cytomegalovirus can directly assemble clotting protein complexes on their surfaces to generate thrombin. This bypasses the normally strict regulation of coagulation imposed by cells. Virus initiated clot formation not only contributes to heart disease, but enhances the susceptibility of host cell infection through protease activated receptors and possibly annexins. Dr. Pryzdial and his lab members are further dissecting the specific host- and virus-derived proteins on the virus surface that trigger coagulation and their role in virus propagation.